Antacids Don't Improve Pulmonary Fibrosis Outcomes

Infections more common in antacid-treated patients with advanced disease

Action Points

Note that this post-hoc analysis of a randomized trial in patients with idiopathic pulmonary fibrosis found that the use of antacid therapy was, in general, not associated with clinical benefit.

Be aware that antacid therapy was not randomized in this setting.

Use of proton pump inhibitors or other antacid therapies does not appear to improve outcomes in patients with idiopathic pulmonary fibrosis (IPF), and the treatment may increase infection risk in patients with advanced disease, according to findings from a post-hoc analysis of three large, randomized trials.

No significant difference in IPF disease progression was seen over a year of follow-up among patients who did and did not receive antacid treatment in the studies of the anti-fibrotic drug pirfenidone (Esbriet).

Adverse event rates were also similar between the antacid and no-antacid groups, but overall infection and pulmonary infection rates were slightly higher in patients treated with proton pump inhibitors, H2 blockers, or both, researcher Michael Kreuter, MD, of the German Center for Lung Research, Heidelberg, and colleagues wrote in Lancet Respiratory Medicine, published online March 31.

Gastroesophageal reflux disease (GERD) is common in patients with idiopathic pulmonary fibrosis, which is a chronic, irreversible, and progressive lung disease with a median survival of 2 to 3 years, the researchers wrote.

They noted that GERD is believed by many to play a role in the development and progression of IPF.

Current clinical practice guidelines for IPF include a conditional recommendation for the use of antacid therapy, while noting that the evidence suggesting an impact on outcomes is limited.

In the newly published analysis, which included pooled data from the placebo groups of three pirfenidone studies (CAPACITY 004 and 006, and ASCEND), researchers analyzed the effects of antacid treatment use from baseline on pulmonary function, exercise tolerance, survival, hospital admission, and adverse events over the course of a year.

The primary endpoint of disease progression was defined as a decrease in predicted forced vital capacity (FVC) by 10% or more, a decrease in 6-minute walk distance (6MWD) by 50 meters or more, or death.

Of the 624 patients randomized to the placebo arms of the three studies, 291 (47%) received antacid therapy and 333 (53%) did not.

Among the main findings from the pooled analysis:

At 52 weeks there was no difference between groups in disease progression (39% in the antacid therapy versus 42% in the no antacid therapy group, P=0·4844), all-cause mortality (7% in both groups, P=0·8947), and IPF-related mortality (4% vs 15%, P=0·4251);

No significant difference was seen between the two groups in absolute FVC decrease by 10% or more (17% versus 19%, P=0·4411), or mean observed change in FVC (% predicted –4·9% [SD 6·4] versus –5·5% [7·2], P=0·3355);

The rate of hospital admission was nonsignificantly higher in the antacid therapy group (22% versus 16%, P=0·0522);

When stratified by baseline FVC (<70% or ≥70%), disease progression, mortality, FVC, 6MWD, and hospital admission did not differ between the groups; and

"Although clinicians might reasonably offer antacid therapy to patients with IPF who have symptomatic gastroesophageal reflux or offer fundoplication to those with uncontrolled reflux symptoms, our data do not suggest that antacids are beneficial as a treatment for IPF," the researchers wrote.

In a commentary published with the analysis, Steven D. Nathan, MD, of Inova Heart and Vascular Institute, Falls Church, Virginia, wrote that while the study "has the inherent limitations of a pooled post-hoc analysis," the large number of patients in the trials is a major strength.

He said that it is not clear if other GERD treatments, such as laparoscopic fundoplication, impact IPF outcomes, or if an as yet unidentified subgroup of patients have better IPF outcomes with antacid treatment.

"In view of the present standard of care in IPF, this new information might be difficult to digest, but like a bad case of gastroesophageal reflux disease, it is not going to go away until we have further data, ideally in the context of a well-designed prospective study that definitively addresses this issue," he wrote.

This research was funded by F. Hoffmann-La Roche.

Kreuter reported receiving grants and personal fees from Boehringer Ingelheim and InterMune/Roche during the conduct of the study.

Nathan reported being a consultant and receiving research funding from Boerhinger-Ingelheim and Roche-Genentech.

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